2.02012-05-31 09:55:17 -06002015-09-13 12:56:05 -0600ECMDB00014M2MDB000003DeoxycytidineDeoxycytidine is one of the principal nucleosides of DNA composed of cytosine and deoxyribose. A nucleoside consists of only a pentose sugar linked to a purine or pyrimidine base, without a phosphate group. When N1 is linked to the C1 of deoxyribose, deoxynucleosides and nucleotides are formed from cytosine and deoxyribose; deoxycytidine monophosphate (dCMP), deoxycytidine diphosphate (dCDP), deoxycytidine triphosphate (dCTP). CTP is the source of the cytidine in RNA (ribonucleic acid) and deoxycytidine triphosphate (dCTP) is the source of the deoxycytidine in DNA (deoxyribonucleic acid).1-(2-Deoxy-b-D-erythro-pentofuranosyl)-cytosine1-(2-Deoxy-b-D-ribofuranosyl)cytosine1-(2-Deoxy-b-delta-erythro-pentofuranosyl)-cytosine1-(2-Deoxy-b-delta-ribofuranosyl)cytosine1-(2-Deoxy-b-δ-erythro-pentofuranosyl)-cytosine1-(2-Deoxy-b-δ-ribofuranosyl)cytosine1-(2-Deoxy-beta-D-erythro-pentofuranosyl)-Cytosine1-(2-Deoxy-beta-D-ribofuranosyl)cytosine1-(2-Deoxy-beta-delta-erythro-pentofuranosyl)-Cytosine1-(2-Deoxy-beta-delta-ribofuranosyl)cytosine1-(2-Deoxy-β-D-erythro-pentofuranosyl)-cytosine1-(2-Deoxy-β-D-ribofuranosyl)cytosine1-(2-Deoxy-β-δ-erythro-pentofuranosyl)-cytosine1-(2-Deoxy-β-δ-ribofuranosyl)cytosine2'-Deoxycytidine2-Deoxy-Cytidine4-Amino-1-(2-deoxy-b-D-erythro-pentofuranosyl)-2(1H)-pyrimidinone4-amino-1-(2-Deoxy-b-delta-erythro-pentofuranosyl)-2(1H)-pyrimidinone4-amino-1-(2-Deoxy-b-δ-erythro-pentofuranosyl)-2(1H)-pyrimidinone4-Amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-2(1H)-pyrimidinone4-Amino-1-(2-deoxy-beta-delta-erythro-pentofuranosyl)-2(1H)-pyrimidinone4-amino-1-(2-Deoxy-β-D-erythro-pentofuranosyl)-2(1H)-pyrimidinone4-amino-1-(2-Deoxy-β-δ-erythro-pentofuranosyl)-2(1H)-pyrimidinoneCytosine deoxyribonucleosideCytosine deoxyribosideD-CytidineDCytDeoxy-CytidineDeoxyribose cytidineDesoxycytidineC9H13N3O4227.2172227.0906059194-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one2'-deoxycytidine951-77-9NC1=NC(=O)N(C=C1)[C@H]1C[C@H](O)[C@@H](CO)O1InChI=1S/C9H13N3O4/c10-7-1-2-12(9(15)11-7)8-3-5(14)6(4-13)16-8/h1-2,5-6,8,13-14H,3-4H2,(H2,10,11,15)/t5-,6+,8+/m0/s1CKTSBUTUHBMZGZ-SHYZEUOFSA-NSolidCytosolExtra-organismPeriplasmlogp-1.93logs-1.16solubility1.59e+01 g/lmelting_point207-210 oClogp-1.9pka_strongest_acidic13.89pka_strongest_basic0.31iupac4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-oneaverage_mass227.2172mono_mass227.090605919smilesNC1=NC(=O)N(C=C1)[C@H]1C[C@H](O)[C@@H](CO)O1formulaC9H13N3O4inchiInChI=1S/C9H13N3O4/c10-7-1-2-12(9(15)11-7)8-3-5(14)6(4-13)16-8/h1-2,5-6,8,13-14H,3-4H2,(H2,10,11,15)/t5-,6+,8+/m0/s1inchikeyCKTSBUTUHBMZGZ-SHYZEUOFSA-Npolar_surface_area108.38refractivity53.03polarizability21.65rotatable_bond_count2acceptor_count6donor_count3physiological_charge0formal_charge0Pyrimidine metabolismThe metabolism of pyrimidines begins with L-glutamine interacting with water molecule and a hydrogen carbonate through an ATP driven carbamoyl phosphate synthetase resulting in a hydrogen ion, an ADP, a phosphate, an L-glutamic acid and a carbamoyl phosphate. The latter compound interacts with an L-aspartic acid through a aspartate transcarbamylase resulting in a phosphate, a hydrogen ion and a N-carbamoyl-L-aspartate. The latter compound interacts with a hydrogen ion through a dihydroorotase resulting in the release of a water molecule and a 4,5-dihydroorotic acid. This compound interacts with an ubiquinone-1 through a dihydroorotate dehydrogenase, type 2 resulting in a release of an ubiquinol-1 and an orotic acid. The orotic acid then interacts with a phosphoribosyl pyrophosphate through a orotate phosphoribosyltransferase resulting in a pyrophosphate and an orotidylic acid. The latter compound then interacts with a hydrogen ion through an orotidine-5 '-phosphate decarboxylase, resulting in an release of carbon dioxide and an Uridine 5' monophosphate. The Uridine 5' monophosphate process to get phosphorylated by an ATP driven UMP kinase resulting in the release of an ADP and an Uridine 5--diphosphate.
Uridine 5-diphosphate can be metabolized in multiple ways in order to produce a Deoxyuridine triphosphate.
1.-Uridine 5-diphosphate interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in the release of a water molecule and an oxidized thioredoxin and an dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate.
2.-Uridine 5-diphosphate interacts with a reduced NrdH glutaredoxin-like protein through a Ribonucleoside-diphosphate reductase 1 resulting in a release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate.
3.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate. The latter compound interacts with a reduced flavodoxin through ribonucleoside-triphosphate reductase resulting in the release of an oxidized flavodoxin, a water molecule and a Deoxyuridine triphosphate
4.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate interacts with a reduced flavodoxin through a ribonucleoside-triphosphate reductase resulting in the release of a water molecule, an oxidized flavodoxin and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate.
5.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP then interacts with a reduced NrdH glutaredoxin-like protein through a ribonucleoside-diphosphate reductase 2 resulting in the release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate.
6.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in a release of a water molecule, an oxidized thioredoxin and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate.
The deoxyuridine triphosphate then interacts with a water molecule through a nucleoside triphosphate pyrophosphohydrolase resulting in a release of a hydrogen ion, a phosphate and a dUMP. The dUMP then interacts with a methenyltetrahydrofolate through a thymidylate synthase resulting in a dihydrofolic acid and a 5-thymidylic acid. Then 5-thymidylic acid is then phosphorylated through a nucleoside diphosphate kinase resulting in the release of an ADP and thymidine 5'-triphosphate.PW000942ec00240MetabolicDrug metabolism - other enzymesec00983Metabolic pathwayseco01100pyrimidine deoxyribonucleosides degradationThe degradation of deoxycytidine starts with deoxycytidine being introduced into the cytosol through either a nupG or nupC symporter.
Once inside, it can can be degrade through water,a hydrogen ion and a deoxycytidien deaminsa resultin in the release of a ammonium and a a deoxyuridine. The deoxyuridine is then degraded through a uracil phosphorylase resulting in the release of a deoxyribose 1-phosphate and a uracil.
The degradation of thymidine starts with thymidine being introduced into the cytosol through either a nupG or nupC symporter.
Thymidine is then degrades through a phosphorylase resulting in the release of a thymine and a deoxyribose 1-phosphate.PW002063Metabolicsalvage pathways of pyrimidine deoxyribonucleotidesThe pathway begins with the introduction of deoxycytidine into the cytosol, either through a nupG symporter or a nupC symporter. Once inside it is deaminated when reacting with a water molecule, a hydrogen ion and a deoxycytidine deaminase resulting in the release of an ammonium and a deoxyuridine. Deoxyuridine can also be imported through a nupG symporter or a nupC symporter.
Deoxyuridine can react with an ATP through a deoxyuridine kinase resulting in the release of a ADP , a hydrogen ion and a dUMP.
Deoxyuridine can also react with a phosphate through a uracil phosphorylase resulting in the release of a uracil and a deoxy-alpha-D-ribose 1-phosphate. This compound in turn reacts with a thymine through a thymidine phosphorylase resulting in the release of a phosphate and a thymidine. Thymidine in turn reacts with an ATP through a thymidine kinase resulting in a release of an ADP, a hydrogen ion and a dTMP PW002061Metabolicsalvage pathways of pyrimidine deoxyribonucleotidesPWY0-181pyrimidine deoxyribonucleosides degradationPWY0-1298Specdb::CMs3171Specdb::CMs37243Specdb::CMs137113Specdb::CMs144847Specdb::CMs1046911Specdb::CMs1046912Specdb::CMs1046914Specdb::CMs1046916Specdb::CMs1046918Specdb::CMs1046920Specdb::CMs1046921Specdb::CMs1046923Specdb::CMs1046925Specdb::CMs1046927Specdb::CMs1046929Specdb::CMs1046931Specdb::CMs1046933Specdb::NmrOneD1029Specdb::NmrOneD1119Specdb::NmrOneD166476Specdb::MsMs22Specdb::MsMs23Specdb::MsMs24Specdb::MsMs2533Specdb::MsMs2534Specdb::MsMs2535Specdb::MsMs2536Specdb::MsMs2537Specdb::MsMs2538Specdb::MsMs2539Specdb::MsMs2540Specdb::MsMs2541Specdb::MsMs2542Specdb::MsMs2543Specdb::MsMs2544Specdb::MsMs2545Specdb::MsMs2546Specdb::MsMs179610Specdb::MsMs179611Specdb::MsMs179612Specdb::MsMs181941Specdb::MsMs181942Specdb::MsMs181943Specdb::MsMs437549Specdb::MsMs437550Specdb::NmrTwoD922HMDB000141371113117C00881DEOXYCYTIDINEDCZDeoxycytidineKeseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590.21097882Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114.22080510van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25.17765195Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948.18331064van den Bosch J, Lubbert M, Verhoef G, Wijermans PW: The effects of 5-aza-2'-deoxycytidine (Decitabine) on the platelet count in patients with intermediate and high-risk myelodysplastic syndromes. Leuk Res. 2004 Aug;28(8):785-90.15203276Lee SH, Jung BH, Kim SY, Chung BC: A rapid and sensitive method for quantitation of nucleosides in human urine using liquid chromatography/mass spectrometry with direct urine injection. Rapid Commun Mass Spectrom. 2004;18(9):973-7.15116424Wepierre J, Marty JP, Chanal JL, Sincholle D: Percutaneous absorption of 5-iodo-2' deoxycytidine in the hairless rat and in man. Eur J Drug Metab Pharmacokinet. 1984 Jan-Mar;9(1):79-83.6714272Coral S, Sigalotti L, Altomonte M, Engelsberg A, Colizzi F, Cattarossi I, Maraskovsky E, Jager E, Seliger B, Maio M: 5-aza-2'-deoxycytidine-induced expression of functional cancer testis antigens in human renal cell carcinoma: immunotherapeutic implications. Clin Cancer Res. 2002 Aug;8(8):2690-5.12171902Olivares J, Verdys M: Isocratic high-performance liquid chromatographic method for studying the metabolism of blood plasma pyrimidine nucleosides and bases: concentration and radioactivity measurements. J Chromatogr. 1988 Dec 29;434(1):111-21.3243806Maley, F. et al., J. Biol. Chem., 1958, 233, 1538-1543, (5-diphosphate)Charubala, R. et al., Synthesis, 1984, 965-968, (5'-(4,4'-dimethoxytrityl) 4N-benzoyl)Schaller, H. et al., J.A.C.S., 1963, 85, 3821-3827, (5'-(4,4'-dimethoxytrityl) 4N-benzoyl)Benz, E. et al., J.O.C., 1965, 30, 3067-3071, (4N-benzoyl, 5'-tosyl, 3',4N-dibenzoyl, 4N,5'-dibenzoyl, 5'-tosyl 4N-benzoyl, 5'-trityl 3',4N-dibenzoyl)Hruska, F.E. et al., Can. J. Chem., 1974, 52, 497-508, (pmr)Jones, A.J. et al., Proc. Natl. Acad. Sci. U.S.A., 1970, 65, 27-30, CA, 72, 96682j, (cmr)Miles, H.T., J.A.C.S., 1963, 85, 1007-1008, (ir, pmr)Young, D.W. et al., Acta Cryst. B, 1975, 31, 961-965, (cryst struct)Michelson, A.M. et al., J.C.S., 1954, 34-40, (phosphates, 3',4N-di-Ac, 5'-trityl, 5'-trityl 3',4N-di-Ac)Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, DAQ850Aldrich Library of 13C and 1H FT NMR Spectra, 1992, 3, 396A, 396C, (nmr)Stawinski, J. et al., Chem. Comm., 1976, 243-244, (3',4N,5'-tribenzoyl)Ulbricht TL. Nucleosides. 3. Synthesis of 1-methyl-2'-deoxycytidine, and comments on the N.m.r. spectra of cytosine nucleosides. J Chem Soc Perkin 1. 1965 Sep:6134-5.Wang Z, Prudhomme DR, Buck JR, Park M, Rizzo CJ. Stereocontrolled syntheses of deoxyribonucleosides via photoinduced electron-transfer deoxygenation of benzoyl-protected ribo- and arabinonucleosides. J Org Chem. 2000 Sep 22;65(19):5969-85. Saneyoshi M, Tohyama J, Nakayama C, Takiya S, Iwabuchi M. Inhibitory effects of 3'deoxycytidine 5'-triphosphate and 3'-deoxyuridine 5'-triphosphate on DNA-dependent RNA polymerases I and II purified from Dictyostelium discoideum cells. Nucleic Acids Res. 1981 Jul 10;9(13):3129-38.FOX JJ, WEMPEN I. Pyrimidine nucleosides. Adv Carbohydr Chem. 1959;14:283-380.Raffaele Saladino, Enrico Mincione, Claudia Crestini, Maurizio Mezzetti. Transformations of thiopyrimidine and thiopurine nucleosides following oxidation with dimethyldioxirane. 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Journal of the American Chemical Society (1961), 83 4066-50. http://hmdb.ca/system/metabolites/msds/000/000/008/original/HMDB00014.pdf?1358461423Protein ushAP07024USHA_ECOLIushAhttp://ecmdb.ca/proteins/P07024.xmlMultifunctional protein surEP0A840SURE_ECOLIsurEhttp://ecmdb.ca/proteins/P0A840.xml5'-nucleotidase yjjGP0A8Y1YJJG_ECOLIyjjGhttp://ecmdb.ca/proteins/P0A8Y1.xmlCytidine deaminaseP0ABF6CDD_ECOLIcddhttp://ecmdb.ca/proteins/P0ABF6.xmlClass B acid phosphataseP0AE22APHA_ECOLIaphAhttp://ecmdb.ca/proteins/P0AE22.xml5'-nucleotidase yfbRP76491YFBR_ECOLIyfbRhttp://ecmdb.ca/proteins/P76491.xmlNucleoside permease nupCP0AFF2NUPC_ECOLInupChttp://ecmdb.ca/proteins/P0AFF2.xmlNucleoside permease nupGP0AFF4NUPG_ECOLInupGhttp://ecmdb.ca/proteins/P0AFF4.xmlNucleoside permease nupXP33021NUPX_ECOLInupXhttp://ecmdb.ca/proteins/P33021.xmlNucleoside-specific channel-forming protein tsxP0A927TSX_ECOLItsxhttp://ecmdb.ca/proteins/P0A927.xmldCMP + Water > Deoxycytidine + PhosphateDeoxycytidine + Hydrogen ion + Water > Deoxyuridine + AmmoniumdCMP + Water <> Deoxycytidine + PhosphateR01664RXN0-5292Deoxycytidine + Water <> Deoxyuridine + AmmoniaR02485Water + Deoxycytidine > Ammonia + DeoxyuridineR02485CYTIDEAM-RXNCytidine + Water + Deoxycytidine <> Uridine + Ammonia + DeoxyuridineR01878